Understanding the mechanisms of pathogenesis and host immunity is critical to the success of developing an effective HIV vaccine. Studies of non-HIV lentiviruses in animals have identified viral pathogenesis factors and host humoral and/or cellular effectors essential to a protective immunity. The protective immunity seen in animals, however, does not always correlate with that in a human infection. An in vivo model for direct evaluation of HIV immunity is urgently needed. In this pilot project, we propose to further explore the human peripheral blood lymphocyte-scid/beige mouse model (hu-PBL-scid/bg) for the evaluation of HIV vaccines and host immunity. Using this model, we have previously shown that multiply exposed, HIV-seronegative individuals have protective immunity could be evoked via vaccination., and the hu-PBL- scid/bg mouse model could be a useful for studies of HIV vaccines and host immunity. Most of the HIV vaccines under clinical trials are based on subunit peptides, recombinant proteins, eukaryotic viral or non-viral vectors. Even through whole viral vaccines have been successfully used for treating various viral diseases, whole-HIV based vaccines have not been tested in humans because of concerns of possible HIV infection. Several HIV-1 vaccine constructs have been generated based on replicative and non-replicative HIV-1 recombinants. In this pilot study, different HIV-1 vaccine constructs will be tested, and the in vivo HI immunity in patients under highly active anti-retroviral therapy (HAART) will also be examined using the scid/beige mouse model. There are two specific aims in this pilot study. 1) To examine primary and secondary immune responses in the hu-PBL- scid/bg mice using antigens including different HIV-1 vaccine constructs; and 2) To assess the immune functions of HAART patients by using the scid/bg in vivo model. Data obtained from this pilot study will be used to support further development of the hu-PBL-scid/bg mouse model.